FGF-2 Modulates the Expression of Nestin in C6 Glioma Cells

CNS traumatic injuries induce a specific gliotic reaction in which astrocytes are involved. In the process of gliotic scar formation, astrocytes regain the ability of proliferation and are called reactive astrocytes. Previous studies have demonstrated that nestin, an intermediate filament proteins, is a differentiation antigen that is presented in radial glia/immature astrocytes and is re-expressed by reactive astrocytes. Our previous study has also shown that reactive astrocytes migrate to the wound area only after the re-expression of nestin. In addition, recent report showed that nestin functions as a survival determinant by sequestering Cdk5/p35 complex and prevent Cdk5 induced apoptosis in neural stem cells. These results indicate that nestin may participate in the pathological responses of reactive astrocytes upon CNS injury. Although substantial researches have been focused on the cellular characteristics of reactive astrocytes, little is known about the factors that induce and regulate the re-expression of nestin. Fibroblast growth factor-2 (FGF-2) is an effective mitogen and is expressed in the developing nervous tissue. It stimulates the proliferation and differentiation of neuroblasts, glial precursor cells and smooth muscle cells, in which nestin are expressed. To examine if FGF-2 is a potent factor that evokes the re-expression of nestin, C6 glioma cells were used as the model system. The results showed that nestin expression is regulated by FGF-2 via de novo protein synthesis. Further signaling analyses also revealed that the FGF-2-induced nestin re-expression is mediated through the activation of the FGFR-MAPK-ERK signaling axis. These findings provide new insights into the regulation of nestin in reactive astrocytes and enable the further studies on the function of nestin in glial scar formation.